Understanding the mechanisms underlying the first cell differentiation events in human preimplantation development is fundamental for defining the optimal conditions for IVF techniques and selecting the most viable embryos for further development. However, our comprehension of the very early events in development is still very limited. Moreover, our knowledge on early lineage specification comes primarily from studying the mouse model. It is important to recognize that although mammalian embryos share similar morphological landmarks, the timing and molecular control of developmental events may vary substantially between species. Mammalian blastocysts comprise three cell types that arise through two sequential rounds of binary cell fate decisions. During the first decision, cells located on the outside of the developing embryo form a precursor lineage for the embryonic part of the placenta: the trophectoderm and cells positioned inside the embryo become the inner cell mass (ICM). Subsequently, ICM cells differentiate into embryonic lineages that give rise to a variety of tissues in the developing foetus: either the epiblast or extraembryonic primitive endoderm. Successful formation of all three lineages is a prerequisite for implantation and development to term. A comprehensive understanding of the lineage specification processes in mammals is therefore necessary to shed light on the causes of early miscarriages and early pregnancy pathologies in humans.